Judith I. Wyatt

EFFECT OF DUODENAL ULCER SURGERY AND ENTEROGASTRIC REFLUX ON GAMPYLOBACTER PYLORIDIS

To assess the effect of duodenal ulcer surgery on Campylobacter pyloridis gastric biopsies were done and fasting bile acid concentrations in gastric aspirates were measured in 35 patients with active duodenal ulceration and 54 who had undergone surgery at some time. Biopsy specimens were assessed blind for the presence of C pyloridis and scored for severity of reflux gastritis by the use of a histological grading system. Among patients who had undergone highly selective vagotomy the proportion who were C pyloridis-positive was similar to that in the unoperated group, but among those who had undergone Billroth I partial gastrectomy, Billroth II partial gastrectomy, or truncal vagotomy and gastroenterostomy it was significantly lower (p less than 0.001). The absence of C pyloridis correlated strongly (p less than 0.001) with high reflux scores and increased bile acid concentrations in the stomach. Reflux scores and bile acid concentrations were significantly higher (p less than 0.01) after Billroth I and Billroth II partial gastrectomies and truncal vagotomy and gastroenterostomy than in the active duodenal ulcer or highly selective vagotomy groups. There was a highly significant correlation (p less than 0.001) between reflux scores and bile acid concentrations. These results suggest that reflux may disrupt mucus and thus cause the death of campylobacters that live beneath it. They also suggest that reflux may produce a reflux-specific gastritis. Highly selective vagotomy may protect against these changes in the gastric mucosa.

Hepatic resection and transplantation for primary carcinoid tumors of the liver.

Objective:To discuss the diagnosis and management of primary carcinoid tumors of the liver in light of our experience and a literature review. Summary Background Data:Carcinoid tumors of the liver are rare and pose a diagnostic and management dilemma. This series is the largest reported and the only one to include liver transplantation as a treatment option. Methods:Between March 1994 and May 2002, we treated 8 patients (4 male, 4 female) with primary hepatic carcinoid tumors. Carcinoid syndrome complicated only 1 of the cases. Treatment was by liver resection in 6 patients and orthotopic liver transplantation in 2. Results:The diagnosis was confirmed histologically with light microscopy and immunohistochemistry in the absence of an alternative primary site. Six patients remain alive and disease free after follow-up of more than 3 years: 39, 43, 45, 50, 50, and 95 months. Two patients are recently postoperative. Conclusions:Active exclusion of an extrahepatic primary site is essential for the diagnosis of primary carcinoid of the liver. The mainstay of treatment should be liver resection, although liver transplantation may be considered in patients with widespread hepatic involvement. A radical surgical approach is warranted as this disease carries a better prognosis than for other primary hepatic tumors and for secondary hepatic carcinoids.

Emergency Subtotal Hepatectomy: A New Concept for Acetaminophen-Induced Acute Liver Failure : Temporary Hepatic Support by Auxiliary Orthotopic Liver Transplantation Enables Long-term Success

Introduction:Acetaminophen (paracetamol) overdose (AOD) has recently emerged as the leading cause of acute liver failure (ALF) in the United States, with an incidence approaching that seen in the United Kingdom. We describe a new way to treat AOD ALF patients fulfilling Kings College criteria for “super-urgent” liver transplantation. Methods:Beginning in June 1998, we have been piloting a clinical program of subtotal hepatectomy and auxiliary orthotopic liver transplantation (ALT) for AOD ALF. Our technique is based on the following principles: (1) subtotal hepatectomy; (2) auxiliary transplantation of a whole liver graft; (3) gradual withdrawal of immunosuppression after recovery. Results were compared with patients who had undergone an orthotopic liver transplantation (OLT) for AOD ALF in the same period. Quality of life comparisons were made using the SF36 questionnaire. Results:Thirteen patients underwent this procedure between June 1998 and March 2005. Median survival is 68 months (range, 0–102 m). Actual survival data show that 9 of 13 patients are alive (69%) compared with 7 of 13 OLT patients (54%). One ALT patient required a retransplantation with an OLT due to hepatic vein thrombosis, and immunosuppression is therefore maintained. The other 8 surviving ALT patients are off immunosuppression. These 8 ALT patients have normal liver function and have a better quality of life compared with the 7 surviving OLT patients. Conclusion:Our results with this new technique are encouraging: 69% actual survival, no long-term immunosuppression requirement, and improved quality of life in the 62% successful cases.

The Role of Serology in the Diagnosis of Campylobacter pylori Infection

Circulating antibodies to Campylobacter pylori in patients with campylobacter-associated gastritis are sufficiently specific to allow serodiagnosis of this condition. This is possible by various techniques, the most convenient being enzyme-linked immunosorbent assay. Applications of serodiagnosis are in two areas--in clinical practice, where proper evaluation is still required, and in epidemiology. Here serodiagnosis shows the prevalence of C. pylori in the general population and in specific population groups. A study of C. pylori and dyspeptic symptoms in a group of healthy blood donors showed a significant association between C. pylori and history of peptic ulceration. However in most donors the gastritis was clinically silent.

Goseki grading in gastric cancer : comparison with existing systems of grading and its reproducibility

A novel grading method which utilises intra‐cellular mucin content and tubular differentiation (the Goseki grade) has been applied to 181 gastric cancers removed in potentially curative resections, and compared to conventional tumour grading (well, moderate, poor differentiation) and the Lauren, Ming and WHO classifications. The Goseki grade is significantly related to patient survival and, unlike the existing approaches, remains so after allowing for tumour stage in multivariate analyses. Potential relationships between the Goseki grade, direct tumour spread, lymph node involvement and survival have been investigated. Prognosis is particularly related to mucin content; 55% of patients with mucin‐rich tumours dying within 5 years compared to 29% of those with mucin‐poor cancers. A smaller proportion of mucin‐poor cancers show lymph node involvement (N1 and N2) than mucin‐rich tumours (52%v. 73%) and a smaller proportion of cancers showing good tubular differentiation exhibit widespread lymph node involvement (N2) than tubule‐poor cancers (11%v. 28%). However, these differences did not achieve statistical significance. When compared to the existing classification or grading methods, the Goseki grade was found to be highly significantly correlated with the WHO and Lauren classifications and to conventional grading, but not to the Ming classification. These inter‐relations are largely dependent upon tubular differentiation. There was no relationship between Goseki grade and the lymphocytic response around the tumour margin. Inter‐observer agreement on the WHO type and the Lauren, Ming and Goseki grading methods was tested on 70 randomly selected cases. Only moderate agreement was achieved with any of these approaches (pairwise kappa values ranging from 0.485–0.565), but when the two‐category situation ‘mucin‐rich’ versus ‘mucin‐poor’ was examined a higher level of reproducibility was achieved (agreement = 81%; K= 0.605) indicating that pathologists can distinguish these prognostically important categories. It seems likely, therefore, that the strength of the association between tumour cell mucin content and survival will outweigh discrepancies introduced by observer variation.

The Role of Campylobacter pylori in the Pathogenesis of Peptic Ulcer Disease

Most patients with peptic ulceration have chronic gastritis, which typically involves predominantly the antrum. The association between Campylobacter pylori-associated gastritis and peptic ulceration has recently been repeatedly demonstrated. Evidence is accumulating that the bacterium plays a causal role in type-B chronic gastritis. C. pylori also colonizes the duodenum when gastric metaplasia is present. It is likely that the inflamed mucosa is more susceptible to ulcerogenic influences affecting either the stomach or duodenum.

Possible Pathogenetic Pathways of Campylobacter pylori in Gastro-duodenal Disease

The exact pathogenic mechanisms involved in Campylobacter pylori associated gastro-duodenal inflammation are unclear. C. pylori adheres to gastric type epithelium and colonisation is associated with a number of ultrastructural abnormalities. Other factors thought important include the marked bacterial urease activity, enzymatic degradation of the mucous layer and possible toxins. The induced inflammatory reaction will also contribute to tissue damage and a breakdown of normal defense mechanisms.

Radical operation for hilar cholangiocarcinoma in comparable Eastern and Western centers: Outcome analysis and prognostic factors

Background: Extensive resection for hilar cholangiocarcinoma is the most effective treatment, but high morbidity and poor prognosis remain concerns. Previous data have shown marked differences in outcomes between comparable Eastern and Western centers. We compared the outcomes of the management for hilar cholangiocarcinoma at one Japanese and one British institution with comparable experience. Methods: Of 298 consecutive patients with hilar cholangiocarcinoma evaluated at Hirosaki University Hospital, Japan and St. Jamess University Hospital, Leeds, UK, 183 underwent radical resection. Clinicopathologic variables and postoperative outcomes were compared. Results: Significant differences were not observed between the Hirosaki and Leeds cohorts in overall outcomes despite several differences in the patient characteristics. Although there was a difference in 90‐day mortality (2.5% vs 13.6%, respectively), disease‐specific 5‐year survival rates were 32.8% and 31.9%, respectively (P = .767). Multivariate analysis identified trisectionectomy (odds ratio = 2.32; P = .010), combined pancreatoduodenectomy (odds ratio = 7.88; P = .010), and perioperative blood transfusion (odds ratio = 1.88; P = .045) were associated with postoperative major complications, while preoperative biliary drainage associated with postoperative major complications, while preoperative biliary drainage (risk ratio = 2.21; P = .018), perioperative blood transfusion (risk ratio = 1.58; P = .029), lymph node metastasis (risk ratio = 2.00; P = .002), moderate/poorly differentiated tumor (risk ratio = 1.72; P = .029), microvascular invasion (risk ratio = 1.63; P = .046), and R1 resection (risk ratio = 1.90; P = .005) were risk factors for poor survival. Conclusion: Disease‐specific survival and prognostic factors were similar in both centers. Meticulous operative technique to avoid perioperative blood transfusion may improve long‐term survival.

Hepatocellular carcinoma in variegate porphyria: a case report and literature review

Variegate porphyria is an autosomal dominant acute hepatic porphyria characterized by photosensitivity and acute neurovisceral attacks. Hepatocellular carcinoma has been described as a potential complication of variegate porphyria in case reports. We report a case of a 48-year-old woman who was diagnosed with hepatocellular carcinoma following a brief history of right upper quadrant pain which was preceded by a few months of blistering lesions in sun-exposed areas. She was biochemically diagnosed with variegate porphyria, and mutational analysis confirmed the presence of a heterozygous mutation in the protoporphyrinogen oxidase gene. Despite two hepatic resections, she developed pulmonary metastases. She responded remarkably well to Sorafenib and remains in remission 16 months after treatment. A review of the literature revealed that hepatocellular carcinoma in variegate porphyria has been described in at least eight cases. Retrospective and prospective cohort studies have suggested a plausible association between hepatocellular carcinoma and acute hepatic porphyrias. Hepatic porphyrias should be considered in the differential diagnoses of hepatocellular carcinoma of uncertain aetiology. Patients with known hepatic porphyrias may benefit from periodic monitoring for this complication.